Precarious development: the uncertain social life of cellular slime molds.

Cellular slime molds are enigmatic and fascinating organisms whose life cycles of both single and multicellular stages have long charmed and perplexed biologists (1). Increasingly, cellular slime molds—of which the most widely studied is Dictyostelium discoideum—have been used as models to study the maintenance of cooperation, but viewed from this perspective, there are puzzles to resolve. Two recent papers (2, 3) reveal a hitherto unrecognized aspect of D. discoideum life history that prompts a rethink of commonly held views concerning the sociobiology of this and related slime molds. D. discoideum lives in soil, decaying leaves, and on animal scat, where it exists for the most part as individual amoeboid cells that feed on bacteria. When starved, the single cells—of sometimes diverse genotypes— aggregate to form an often chimeric multicellular slug that undergoes morphogenesis and differentiation culminating in the production of a mass of spores suspended at the tip of a stalk. Spores presented in this way are readily dispersed by soil invertebrates. Given appropriate conditions, spores germinate, produce amoebae, and thus complete the life cycle. No such possibility for regeneration is provided to stalk cells: cells fated to become stalk die in the process of fruit body formation (1). The seemingly self-sacrificial nature of stalk cells is interesting from both developmental and evolutionary perspectives. In the context of multicellular organisms more generally, self-sacrificial behavior is nothing new. In metazoans, for example, cells that comprise soma are, like the stalk cells of slime molds, an evolutionary dead end. The primary purpose of soma is to ensure perpetuation of the germ line; indeed, development of soma is crucially dependent on apoptosis. However, there is a big difference between multicellularity in metazoans and multicellularity in slime molds that makes cell death understandable in metazoans but less so in slime molds. This difference concerns the mode of formation of the multicellular entity (4). In metazoans, the multicellular stage typically arises from a single cell (a fertilized egg). In slime molds, the multicellular stage is an aggregate of sometimes unrelated genotypes. From an evolutionary perspective, development of a multicellular entity from a single cell ensures that cells of the organism are derived from a single genotype (thus ensuring perfect relatedness) and limits the possibility that conflicts arising during the life time of the individual are passed to future generations (5). In slime molds, formation of the multicellular entity by aggregation of different genotypes is a sure-fire recipe for conflict (6): in any given chimera, selection is expected to favor those types that take unfair advantage of altruists (those genotypes that invest more in stalk cells). Such “cheater” types threaten persistence of altruists. How self-sacrificial behavior is thus maintained in the face of conditions that would seem to select for its elimination has motivated numerous studies (7). The likelihood of conflict is more than just a theoretical notion. Studies going back several decades provide experimental evidence that cheats exist in nature (8), and linear hierarchies of competitors have been reported (9). Such interactions should limit genetic diversity in natural populations, but this is at odds with reports of high diversity and coexistence of genotypes (10).